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FLASH GENE
Symbol ZNF423 contributors: mct/ - updated : 22-05-2015
HGNC name zinc finger protein 423
HGNC id 16762
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a BMP-signaling module formed by two clusters of fingers
  • 30 Krüppel-like zinc fingers that are organized into discrete clusters
    • HOMOLOGY
    Homologene
    FAMILY
  • krueppel C2H2-type zinc-finger protein family
    • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • transcriptionnally activating the homeobox regulator, that may have multiple roles in signal transduction during development
  • can alter the intensity and duration of the BMP stimulus through SMAD6 and indicate that the tissue-specific expression of ZNF243 is a critical determinant of the cellular response to the BMP signal
  • required for normal cerebellar development
  • having a role as a SMAD cofactor in the context of mesodermal patterning
  • component critically required for retinoic acid (RA)-induced differentiation
  • multiple zinc-finger transcription factor involved in both OE/EBF and BMP-signaling pathways, and required for the proper formation of forebrain and hindbrain midline structures (may be having a pivotal role in CNS midline patterning)
  • required for normal cerebellar development
  • required for patterning the development of neuronal and glial precursors in the developing brain, particularly in midline structures
  • has a key role in coordinating the expression of immature and mature stage-specific genes
  • participates in a developmental switch regulating the transition from differentiation to maturation in olfactory-receptor neurons
  • critical cofactor required for RAR/RXR function and is also crucial for RA-mediated growth arrest and differentiation in neuroblastoma cell lines
  • acts to integrate BMP and Notch signaling, selectively promoting their convergence onto the HES5 gene promoter
  • may help maintain a pool of HES5 positive neurogenic progenitors in the developing neural tube
  • role as a cell-autonomous modifier of Notch signal transduction
  • transcriptional activator of PPARG and inducer of adipogenic determination
  • is the key transcription factor committing cells to the adipogenic lineage, with exceptionally dense CpG sites in its promoter
  • regulates early adipogenic differentiation in fetal progenitor cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    BMP-SMAD and olf pathways
    a component
  • forms a cytosolic complex with the peroxisome proliferator-activated receptor gamma (PPARG) transcriptional activator zinc finger protein 423 (ZNF423)
    • INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • SMADs (in response to bone morphogenetic protein-2 [BMP-2])
  • binds to and negatively regulates EBF1, a basic helix-loop-helix transcription factor required for B-cell lineage commitment and olfactory epithelium development
  • associates with the RARalpha/RXRalpha nuclear receptor complex and is essential for transactivation in response to retinoids
  • interacts with the NOTCH1 intracellular domain in mammalian cell lines, to activate the expression of the NOTCH1 target HES5
  • ZFP423 interacts with the HES5 promoter
  • BMP4 was also able to increase ZFP423 gene activation, adding another layer of cross-talk in promoting adipogenic differentiation
  • canonical WNT signaling inhibits adipogenic commitment and differentiation through WISP2, which retains ZNF423 in the cytosol
  • appeared to be an estrogen-inducible BRCA1 transcription factor
    • cell & other
    REGULATION
    repressed by ZNF521 that is the intrinsic repressor of ZNF423 and hence of adipocyte commitment during BMP-induced mesenchymal precursor differentiation
    ASSOCIATED DISORDERS
    corresponding disease(s) NPHP14
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by RNA interference in neuroblastoma cells results in a growth advantage and resistance to RA-induced differentiation with poor outcome
    tumoral     --low  
    with NF1, in neuroblastomas with poor outcome
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Homozygous Zfp423 null mice are runted and ataxic, the cerebellum is underdeveloped, and the vermis is severely reduced
  • Zfp423 null mice develop a profound hypoplasia of the cerebellar vermis, reminiscent of the Dandy-Walker malformation